Brain Starts Female and Represses Masculinizing to Stay A Girl

The developing mammalian brain is destined for a female phenotype unless exposed to gonadal hormones during a perinatal sensitive period…Our data show that brain feminization is maintained by the active suppression of masculinization via DNA methylation.

In sexually reproducing species, the developing brain is either masculinized or feminized in a manner that assures adult neural physiology and reproductive behavior are consistent with the differentiated gonads. In mammals, feminization of the brain is independent of the ovary and therefore considered a default developmental pathway that does not require active secretion of ovarian steroids. Masculinization is the differentiation away from the female phenotype and is mediated by gonadal steroids generated by the fetal testis during a perinatal sensitive period…

The most robust and reliable brain sexual dimorphisms are found in the preoptic area, consistent with its central role in male copulatory behavior and control of gonadotropin secretion from the anterior pituitary…All of these changes are established in the first few days following birth and endure until adulthood, but it has been unknown how these developmental, hormonally induced changes in the brain are maintained across the lifespan…rather than the male genetic program simply not being induced, it is instead actively suppressed in the female by a female ­specific pattern of gene methylation…